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New drugs in phase I and beyond workshop. 处于I期及以后阶段的新药。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7343-7_19
R Griffiths, C Lanni
{"title":"New drugs in phase I and beyond workshop.","authors":"R Griffiths, C Lanni","doi":"10.1007/978-3-0348-7343-7_19","DOIUrl":"https://doi.org/10.1007/978-3-0348-7343-7_19","url":null,"abstract":"","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"47 ","pages":"177-9"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18784867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mediation of inflammation by cyclooxygenase-2. 环氧化酶-2介导炎症。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7276-8_5
K Seibert, J Masferrer, Y Zhang, S Gregory, G Olson, S Hauser, K Leahy, W Perkins, P Isakson
{"title":"Mediation of inflammation by cyclooxygenase-2.","authors":"K Seibert,&nbsp;J Masferrer,&nbsp;Y Zhang,&nbsp;S Gregory,&nbsp;G Olson,&nbsp;S Hauser,&nbsp;K Leahy,&nbsp;W Perkins,&nbsp;P Isakson","doi":"10.1007/978-3-0348-7276-8_5","DOIUrl":"https://doi.org/10.1007/978-3-0348-7276-8_5","url":null,"abstract":"<p><p>Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.</p>","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"46 ","pages":"41-50"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18616458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 158
Effects of prolonged L-arginine administration on blood pressure in patients with essential hypertension (EH). 延长l -精氨酸给药对原发性高血压患者血压的影响。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7346-8_22
M Malczewska-Malec, P Goldsztajn, K Kawecka-Jaszcz, D Czarnecka, A Siedlecki, T Siemienska, A Dembinska-Kiec
{"title":"Effects of prolonged L-arginine administration on blood pressure in patients with essential hypertension (EH).","authors":"M Malczewska-Malec,&nbsp;P Goldsztajn,&nbsp;K Kawecka-Jaszcz,&nbsp;D Czarnecka,&nbsp;A Siedlecki,&nbsp;T Siemienska,&nbsp;A Dembinska-Kiec","doi":"10.1007/978-3-0348-7346-8_22","DOIUrl":"https://doi.org/10.1007/978-3-0348-7346-8_22","url":null,"abstract":"<p><p>L-arginine (L-Arg) was administered intravenously through 4 consecutive days to 20 males (40-63 years old) with essential hypertension (EH). Significant decrease (p < 0.02) of systolic blood pressure (SBP) was observed only during the first day of the therapy and tachyphylaxis against L-Arg was noticed. The reduction of diastolic blood pressure (DBP) was more marked (p < 0.001). Significant changes in cGMP plasma level and the nitrite/nitrate urine concentration were not observed. L-Arg caused a significant activation of fibrinolysis (p < 0.005). The decrease of platelet activity, measured by the ADP-induced aggregation, after L-Arg administration was not statistically significant. Therefore, L-Arg may play only a secondary role in the treatment of EH.</p>","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"45 ","pages":"157-62"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18718515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
The similarity in action of hypoxia and platelet-activating factor on smooth muscle cells of coronary arteries: possible explanation for hypoxic coronary spasm development. 缺氧和血小板活化因子对冠状动脉平滑肌细胞作用的相似性:对缺氧冠状动脉痉挛发展的可能解释。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7346-8_37
A Soloviev, P Braquet
{"title":"The similarity in action of hypoxia and platelet-activating factor on smooth muscle cells of coronary arteries: possible explanation for hypoxic coronary spasm development.","authors":"A Soloviev,&nbsp;P Braquet","doi":"10.1007/978-3-0348-7346-8_37","DOIUrl":"https://doi.org/10.1007/978-3-0348-7346-8_37","url":null,"abstract":"<p><p>Studies in isolated smooth muscles and single cells of coronary arteries have demonstrated that both hypoxia and platelet activating factor (PAF) in a similar manner increased contractile force and Ca-activated K currents. The specific antagonists of PAF receptors BN 52021 and WEB 2886 significantly decreased contractile responses of vascular smooth muscle (VSM) to PAF and hypoxia. Taken together, these data allow to suggest that endogenous PAF can produce both phasic and tonic contraction in coronary arteries under hypoxic condition.</p>","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"45 ","pages":"275-82"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18721088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vasodilator effects of PGE1 in the coronary and systemic circulation of the rat are mediated by ATP-sensitive potassium (K+) channels. PGE1在大鼠冠状动脉和体循环中的血管扩张作用是通过atp敏感的钾离子通道介导的。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7346-8_11
P Ney, M Feelisch
{"title":"Vasodilator effects of PGE1 in the coronary and systemic circulation of the rat are mediated by ATP-sensitive potassium (K+) channels.","authors":"P Ney,&nbsp;M Feelisch","doi":"10.1007/978-3-0348-7346-8_11","DOIUrl":"https://doi.org/10.1007/978-3-0348-7346-8_11","url":null,"abstract":"<p><p>This study was undertaken to investigate the possible involvement of K+ channels in PGE1-mediated vasodilatation. The increase in coronary flow elicited by PGE1 in isolated working rat hearts was attenuated by phentolamine and glibenclamide, inhibitors of ATP-regulated K+ channels, whereas apamin and charybdotoxin, inhibitors of calcium-activated K+ channels, were ineffective. In the anaesthetized rat, the duration of the hypotensive action of PGE1 was markedly attenuated by glibenclamide. It is concluded that the vasodilatory action of PGE1 in the coronary and systemic circulation of the rat is, at least in part, mediated via an opening of ATP-sensitive K+ channels.</p>","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"45 ","pages":"71-6"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18544616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Molecular regulation and augmentation of prostacyclin biosynthesis. 前列环素生物合成的分子调控与增强。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7346-8_2
K K Wu
{"title":"Molecular regulation and augmentation of prostacyclin biosynthesis.","authors":"K K Wu","doi":"10.1007/978-3-0348-7346-8_2","DOIUrl":"https://doi.org/10.1007/978-3-0348-7346-8_2","url":null,"abstract":"<p><p>Prostacyclin is a major vasoprotective molecule. It has multiple physiological functions. Its synthesis is determined by several enzymes of which cyclooxygenase (COX) plays a key role. Two isoforms of COX have been identified. Their expression and regulation are controlled by different mechanisms. COX-1 is constitutively expressed and physiologically important. PGI2 synthesis can be augmented by virus-mediated transfer COX-1 gene. This strategy may be useful for therapy of vascular thrombosis and tissue ischemia.</p>","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"45 ","pages":"11-7"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18718601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Metabolism and excretion of nitric oxide in man: basal studies and clinical applications. 人体一氧化氮的代谢和排泄:基础研究和临床应用。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7346-8_18
A Wennmalm
{"title":"Metabolism and excretion of nitric oxide in man: basal studies and clinical applications.","authors":"A Wennmalm","doi":"10.1007/978-3-0348-7346-8_18","DOIUrl":"https://doi.org/10.1007/978-3-0348-7346-8_18","url":null,"abstract":"","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"45 ","pages":"129-38"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18718603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
Exogenously supplied nitric oxide influences the dilation of the capillary microvasculature in vivo. 外源性一氧化氮影响体内毛细血管的扩张。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7346-8_21
W Bloch, D Hoever, D Reitze, L Kopalek, K Addicks
{"title":"Exogenously supplied nitric oxide influences the dilation of the capillary microvasculature in vivo.","authors":"W Bloch,&nbsp;D Hoever,&nbsp;D Reitze,&nbsp;L Kopalek,&nbsp;K Addicks","doi":"10.1007/978-3-0348-7346-8_21","DOIUrl":"https://doi.org/10.1007/978-3-0348-7346-8_21","url":null,"abstract":"<p><p>An endogenous NO-release which exceeds the basal endogenous NO-release has a regulatory effect on capillary microvasculature in isolatedly perfused rat hearts. The basal NO-release in contrast has no effect on capillaries. The functional findings are corresponding to the endothelial distribution of NOS in coronary vessels, which displays a lack of NOS in capillary endothelium. An increase of coronary flow by exogenously administered NO-donors does not necessarily lead to a dilation of capillary microvasculature. Local differences in the release of unstable NO by SNP and GTN are responsible for variations in effects. We can conclude: NO influences the dilation of the capillary microvasculature independently of flow regulation.</p>","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"45 ","pages":"151-6"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18718606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Rapid tolerance to formation of authentic NO from nitroglycerin in vivo. 体内对硝化甘油形成真NO的快速耐受性。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7346-8_31
M G Persson, P Agvald, L E Gustafsson
{"title":"Rapid tolerance to formation of authentic NO from nitroglycerin in vivo.","authors":"M G Persson,&nbsp;P Agvald,&nbsp;L E Gustafsson","doi":"10.1007/978-3-0348-7346-8_31","DOIUrl":"https://doi.org/10.1007/978-3-0348-7346-8_31","url":null,"abstract":"<p><p>Direct evidence for in vivo NO formation from nitroglycerin (GTN) was obtained by measurements of exhaled nitric oxide in anaesthetized. Infusions of GTN (1-100 micrograms kg-1 min-1 i.v.) induced dose-dependent and biphasic increments in exhaled NO parallelled by reductions in systemic blood pressure. The NO detected during GTN infusion was unaffected by the nitric oxide synthase inhibitor L-NAME or acute i.v. administration of L-cysteine, N-acetyl-L-cysteine or glutathione. The present data demonstrate that NO is formed from GTN in vivo, and that tolerance in vivo is due to decreased formation of NO.</p>","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"45 ","pages":"213-7"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18719111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Potential phospholipase A2s involved in inflammatory diseases. 参与炎性疾病的潜在磷脂酶A2s。
Agents and actions. Supplements Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-7276-8_4
E A Dennis
{"title":"Potential phospholipase A2s involved in inflammatory diseases.","authors":"E A Dennis","doi":"10.1007/978-3-0348-7276-8_4","DOIUrl":"https://doi.org/10.1007/978-3-0348-7276-8_4","url":null,"abstract":"","PeriodicalId":7491,"journal":{"name":"Agents and actions. Supplements","volume":"46 ","pages":"35-9"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18615895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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